Systemic inflammation is linked to ischemic stroke and transient ischemic attack (TIA). Cerebral ischemia produces many endogenous ligands and cytokines that elicit an immune response (Arumugam, et al., Shock. (2009) 32:4-16). Leukocytes, including neutrophils and monocytes, are activated and recruited to initiate processes of containment, removal, and repair. We have previously demonstrated in a rat model of TIA that a peripheral immune response occurs to transient brain ischemia with similarities to that observed in experimental brain infarction (Zhan, et al., J Cereb Blood Flow Metab. (2010) 30:110-118; Zhan, et al., Brain Res. (2008) 1234:183-197). This suggests that aspects of the immune response to cerebral ischemia in TIA and stroke are common and may be useful in identifying ischemic events.
In clinical practice, deciphering whether a transient neurological event (TNE) is of ischemic or nonischemic etiology is often difficult. Many common neurological conditions mimic the symptoms of TIA, including migraine, seizure, and syncope. The transient nature of TIA adds to the diagnostic challenge as objective deficits generally resolve by the time of presentation and assessment of symptoms is reliant on patient recall and physician interpretation. Current diagnostic tests including neuroimaging, electrocardiogram, and electroencephalogram are frequently unremarkable, leaving the cause of a TNE unclear. As a result, TIA is estimated to be incorrectly diagnosed in as many as 50% of cases (Ferro, et al., Stroke. (1996) 27:2225-2229; Kraaijeveld, et al., Stroke. (1984) 15:723-725; Castle, et al., Stroke. (2010) 41:1367-1370; Bos, et al., JAMA. (2007) 298:2877-2885; and Johnston S C. JAMA. (2007) 298:2912-2913). However, correctly identifying ischemic TNE is critical as the risk for stroke is high in TIA and can be reduced by early initiation of stroke prevention therapy (Rothwell, et al., Lancet. (2007) 370:1432-1442). Additionally, identifying nonischemic TNE (which have a very low risk of stroke) will improve risk stratification and use of health care resources. Thus, improved methods to distinguish ischemic from nonischemic causes of TNE are needed.
Previous studies have demonstrated an immune response in patients with stroke by evaluating leukocyte RNA expression using whole genome microarrays (Barr, et al., Neurology. (2010) 75:1009-1014; Jickling, et al. Ann Neurol. (2010) 68:681-692; and Stamova, et al., Stroke. (2010) 41:2171-2177). However, the distinction between immune response to cerebral ischemia and cerebral infarction was unclear. We report herein the pathways associated with the peripheral immune response to cerebral ischemia, which has clinical utility to identify ischemic causes of TNE.